Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6GBUFA)

• DOT Name: C-C chemokine receptor type 3 (CCR3)
• Synonyms: C C CKR3; C-C CKR-3; CC-CKR-3; CCR-3; CCR3; CKR 3; CKR3; Eosinophil eotaxin receptor; CD antigen CD193
• Gene Name: CCR3
• UniProt ID: CCR3_HUMAN
• PDB ID: 7X9Y
• Pfam ID: PF00001
• Sequence:
  MTTSLDTVETFGTTSYYDDVGLLCEKADTRALMAQFVPPLYSLVFTVGLLGNVVVVMILI
  KYRRLRIMTNIYLLNLAISDLLFLVTLPFWIHYVRGHNWVFGHGMCKLLSGFYHTGLYSE
  IFFIILLTIDRYLAIVHAVFALRARTVTFGVITSIVTWGLAVLAALPEFIFYETEELFEE
  TLCSALYPEDTVYSWRHFHTLRMTIFCLVLPLLVMAICYTGIIKTLLRCPSKKKYKAIRL
  IFVIMAVFFIFWTPYNVAILLSSYQSILFGNDCERSKHLDLVMLVTEVIAYSHCCMNPVI
  YAFVGERFRKYLRHFFHRHLLMHLGRYIPFLPSEKLERTSSVSPSTAEPELSIVF
• Function: Receptor for C-C type chemokine. Binds and responds to a variety of chemokines, including CCL11, CCL26, CCL7, CCL13, RANTES(CCL5) and CCL15. Subsequently transduces a signal by increasing the intracellular calcium ions level. In addition acts as a possible functional receptor for NARS1 ; (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.
• Tissue Specificity: In eosinophils as well as trace amounts in neutrophils and monocytes.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Viral protein interaction with cytokine and cytokine receptor (hsa04061)
  Chemokine sig.ling pathway (hsa04062)
  Human cytomegalovirus infection (hsa05163)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  Chemokine receptors bind chemokines (R-HSA-380108)

Molecular Interaction Atlas (MIA) of This DOT

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of C-C chemokine receptor type 3 (CCR3).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of C-C chemokine receptor type 3 (CCR3).	[2]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of C-C chemokine receptor type 3 (CCR3).	[3]
Aspirin	DM672AH	Approved	Aspirin increases the expression of C-C chemokine receptor type 3 (CCR3).	[4]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of C-C chemokine receptor type 3 (CCR3).	[5]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of C-C chemokine receptor type 3 (CCR3).	[6]
Tacrolimus	DMZ7XNQ	Approved	Tacrolimus decreases the expression of C-C chemokine receptor type 3 (CCR3).	[7]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of C-C chemokine receptor type 3 (CCR3).	[8]

References

• [1] Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome. Blood. 2009 Dec 24;114(27):5512-21. doi: 10.1182/blood-2009-02-204834. Epub 2009 Oct 14.
• [2] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [3] [Inhibitory effects of Galectin-3 on the inflammatory cytokines and chemokines in guinea pig asthma models]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 May;36(3):355-8.
• [4] Association of the CCR3 gene polymorphism with aspirin exacerbated respiratory disease. Respir Med. 2010 May;104(5):626-32. doi: 10.1016/j.rmed.2009.11.024. Epub 2009 Dec 21.
• [5] Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils. J Biol Chem. 2002 Jul 19;277(29):26012-20. doi: 10.1074/jbc.M201803200. Epub 2002 Apr 29.
• [6] Differential regulation of CC chemokine receptors by 9-cis retinoic acid in the human mast cell line, HMC-1. Life Sci. 2006 Aug 22;79(13):1293-300. doi: 10.1016/j.lfs.2006.03.046. Epub 2006 Apr 22.
• [7] Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in atopic dermatitis. Br J Dermatol. 2005 Jun;152(6):1173-81. doi: 10.1111/j.1365-2133.2005.06474.x.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.